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Incidence of antibodies to protamine sulfate/heparin complexes incardiac surgery patients and impact on platelet activation and clinical outcome

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: https://doi.org/10.1160/TH12-11-0844
Issue: 2013: 109/6 (June) pp. 977–1185
Pages: 1141-1147

Incidence of antibodies to protamine sulfate/heparin complexes incardiac surgery patients and impact on platelet activation and clinical outcome

C. Pouplard (1, 2), D. Leroux (1, 2), J. Rollin (1, 2), J. Amiral (3), M.-A. May (4), Y. Gruel (1, 2)

(1) Department of Haematology-Haemostasis, University Hospital of Tours, Tours Cedex, France; (2) UMR CNRS 7292 and François Rabelais University, Tours, France; (3) Hyphen Biomed, Neuville sur Oise, France; (4) Department of Cardiac Surgery, University Hospital of Tours, Tours Cedex, France

Keywords

Heparin-induced thrombocytopenia, cardiac surgery, Protamine, Heparin-dependent antibodies

Summary

A new ELISA (Zymutest HIA®), based on incubation of diluted plasma with protamine/heparin (PRT/H) complexes without and with platelet factor 4 (PF4) provided by a platelet lysate, was used to detect heparin-dependent antibodies in a cohort of 232 cardiac surgery (CS) patients and in 47 patients with heparin-induced thrombocytopenia (HIT). Significant binding of IgG/A/M to PRT/H complexes was demonstrated in 59 CS patients (25.4%), with similar absorbances whether platelet lysate was added to the plasma or not, and significant reactivity to PF4/H in 29 of them. Antibodies to PRT or heparin alone were present in 15 and two of these patients, respectively. Importantly, antibodies to PRT/H were detected in only three of the 47 HIT patients, who had also undergone recent CS. The Zymutest HIA® was positive in another 41 CS patients (17%), but only or mainly when their plasma was tested with platelet lysate, with significant levels of antibodies to PF4/H in 40 of them without detectable reactivity to PRT or heparin alone. Slight antibody binding to PRT/H complexes was also measured in six of these 41 patients. Therefore, a total of 35 CS patients exhibited dual antibody reactivity towards PRT/H and PF4/H complexes. Serotonin release assay performed with PRT alone was positive in 17 CS patients with antibodies to PRT/H, but all had normal platelet count evolution without thrombosis postoperatively. In conclusion, antibodies to PRT/H are frequently present in CS patients postoperatively (25.4%), and can activate platelets in vitro, but their clinical impact remains questionable.

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